Cardiovascular disease is the leading cause of morbidity and mortality in the United States, accounting for approximately 1 million deaths per year. The objective of the Phase I pre-clinical studies outlined in this fasttrack STTR proposal is to validate the proposed methods of isolation, characterization, and administration of preferred progenitor cell preparations. The overall goal of the clinical research summarized in the Phase II section of this fast-track STTR project is to begin a progression of human clinical trials to demonstrate the safety and efficacy of Arteriocyte's cellular therapy, using a combination of non-embryonic stem cell populations to create new blood vessels in patients with coronary artery ischemia. The key hypothesis underlying this work is that early AC133+ hemangioblasts, rather than mature endothelial cells, are the critical cells that home to sites of vascular injury and mediate new vessel formation. The clinical trial springing from the project team's preliminary data is to investigate whether intra-coronary infusion of escalating doses of AC133-selected autologous marrow-derived stem cells is reasonably safe for use in humans with coronary artery ischemia, and if this treatment shows any improvement in coronary perfusion. Pre-clinical studies for Arteriocyte's cellular therapy to treat arterial ischemia will be completed during Phase I of this STTR project, with a clear focus on validation of the processes by which cells are selected from bone marrow and then infused via catheter into coronary arteries. The company's overall commercialization plan focuses on developing "off the shelf" products based on umbilical-cord blood stem cells (using its proprietary technology) that can be made available in a timely and effective manner to manage coronary artery disease. Because of the potential for procedural simplicity and robust, long-term benefits, this type of cellular therapy for treating cardiac ischemia is expected to become a major adjuvant modality to current revascularization interventions.